Our preliminary studies indicated that water-soluble antifungal antimicrobics (amphotericin B methyl ester; 6-fluorocytosine) successfully penetrated human fibrin clots infected with Candida albicans, whereas water-insoluble, colloidal drugs (amphotericin B; micronazole) failed to do so. Using this infected fibrin clot model, we plan to examine: 1) different concentrations of antifungal agents; 2) combinations of antifungal antimicrobics; 3) newer drugs; 4) physico-chemical methods for assessment of the penetration of antifungal antimicrobics; 5) different kinds of fungi. Experimental candidal infective endocarditis has been induced in two non-human primates, both rhesus monkeys Macada mulatta. We plan to determine the natural history of untreated experimental infective fungal endocarditis in rhesus and cynomologous Macaca fascieularis monkeys caused by C. albicans, candida parapsilosis, and Aspergillus fumigatus. Having determined the course of experimental infective fungal endocarditis, we will then evaluate treatment using the antifungal antimicrobics studies in fibrin clots.